BACKGROUND Gammadelta T lymphocytes are an important component of innate immunity. Previous studies have shown their role in the development of Crohn's-like colitis in mice. OBJECTIVE The aim of this study was to measure the γδ T lymphocyte levels in Crohn's disease (CD) patients. METHODS A prospective study of 40 patients with CD compared with 40 healthy subjects (control group) matched by age and sex was undertaken. Lennard-Jones criteria were used for the diagnosis of CD. Disease activity was measured with the Crohn's disease activity index (CDAI). New patients, patients in remission, and patients with active disease were evaluated. Lymphocytic populations of CD3+, CD4+, CD8+, CD56+, CD19+, and αβ and γδ subsets were measured in the peripheral blood of all participants. RESULTS The levels of CD3+, CD4+, CD8+, and CD19+ lymphocytes were decreased in CD patients compared with the control group (P = 0.002, 0.049, 0.003, and 0.023, respectively). Although both γδ and αβ T lymphocytes were lower in patients with CD, γδ T subsets showed the lowest levels in CD patients (mean 0.0259 × 10(9)/l) versus healthy controls (mean 0.0769 × 10(9)/l), P < 0.001. In particular, γδ CD8+ T subsets (mean 0.0068 × 10(9)/l) had the largest difference compared to the control group (mean 0.0199 × 10(9)/l), P = 0.008. CONCLUSIONS There is a decrease in the global lymphocyte population in the peripheral blood of patients with CD compared to healthy controls. This decrease is more evident in γδ T lymphocytes, especially γδ CD8+ T subsets. Our conclusion is that these results support the theory that a complex alteration of immune responses that affects the total numbers and function of γδ T cells is present in CD.